Chambers are used in many industries including the food and drug industries for many different purposes; freeze drying and sterilization are two such purposes. Freeze dryers used in the pharmaceutical and other industries traditionally include a freeze dryer chamber, shelves in the chamber for holding the product(s) to be freeze dried, a condenser with refrigerator coils, a vacuum system, and piping for connecting the freeze dryer components. Generally, the freeze dryer shelves are heated and cooled during the freeze drying cycle with heating and cooling means, such as a heat transfer fluid circulating through the shelves and a heat exchanger.
Typically, the products to be freeze dried are in loosely capped containers, which are then placed on the freeze dryer shelves. After the chamber door is closed, the shelves are cooled to about -40.degree. C. to freeze the product. Thermocouples, or other temperature probes, indicate when the product is frozen and at the correct temperature. The freeze dryer chamber and condenser are then evacuated through a top, side or rear port on the condenser to a deep vacuum of about 200 microns of Hg (1 Torr=1000 micron of Hg=1 mm of Hg) while the condenser coils are cooled to around -40.degree. C. As sublimation of moisture from the product occurs, it cools the product further. The shelves are warmed to maintain the frozen product at the desired temperature.
The vaporous moisture from the product escapes from the loosely capped containers and is drawn in vapor form from the containers in the chamber to the condenser. In the condenser, the vapor condenses and then freezes on the condenser coils.
This process continues until the product is sufficiently freeze dried as determined by known means. The chamber is vented to atmospheric pressure, the containers are capped (if it is desired), the chamber door is opened, and the freeze dried product removed.
Traditionally, the condenser is defrosted before the next freeze drying cycle using water or steam. The water or steam may be flowed through the condenser or it may be used to flood the condenser. The chamber is typically isolated from the condenser during this process by a large butterfly or mushroom valve. The condenser is drained at the end of the defrost. The chamber is typically Cleaned-In-Place (C.I.P.) either manually or automatically between each load to remove any debris from the previous load.
Decontamination and sterilization of the chambers is currently accomplished using formaldehyde vapor, ethylene oxide gas, peracetic acid, liquid hydrogen peroxide, or steam. Each of these methods presents serious disadvantages. For the purposes of this invention the term decontamination means a 3 log (or greater) reduction in bioburden and sterilization means a 6 log (or greater) reduction in bioburden.
Methods using formaldehyde vapor and ethylene oxide gas typically operate at pressures below 15 psig and at temperatures below 140.degree. F.; however, the sterilizing agents are undesirable because they are considered carcinogenic and may be harmful to the operator. Residual removal is also a problem. Ammonia is used to neutralize the formaldehyde gas, leaving a white powder distributed throughout the freeze dryer which is difficult to remove without compromising sterility.
Ethylene oxide vapors can be removed and catalyzed during a lengthy aeration (i.e. more than 8 hours); however, various air/ethylene oxide mixtures which are present during the decontamination/sterilization process are explosive. Consequently, ethylene oxide is typically mixed with Freon 12, an ozone depletor which must be recovered at great expense.
Peracetic acid and liquid hydrogen peroxide may also be sprayed manually, or automatically, throughout the interior of freeze dryers. This method, though, is ineffective on inaccessible areas such as the condenser and "dead legs" (dead-ended piping or lumens) in the freeze dryer unit. Completely flooding the freeze dryer is also not effective since air pockets will prevent the liquid from penetrating into many of the same inaccessible areas.
Steam is emerging as the method of choice. Steam sterilization, however, is achieved at very high temperatures and pressures. As a result, this method requires that the freeze dryer chamber, condenser and associated piping be subjected to high temperature and pressure. The combined high pressure and temperature of steam sterilization (e.g., 250.degree. F. and 15 psig) when alternated with freeze drying while deeply evacuated (at -40.degree. F. and at approximately 200 microns of Hg absolute) takes its toll on the reliability of the freeze dryer system. Furthermore, existing freeze dryers which do not meet the required temperature/pressure requirements cannot be retrofit for steam decontamination/sterilization.
There is a need for a method which can decontaminate or sterilize chambers, particularly freeze dryers, in an economical and simple manner. There is a further need for a method for decontaminating or sterilizing chambers, particularly freeze dryers, that can be applied on existing chambers and freeze dryers. There is also a need for a method for decontaminating or sterilizing chambers particularly freeze dryers, without using hazardous sterilants or chemicals having hazardous decomposition products which are harmful to the environment.